Human hematopoietic microenvironments

PLoS One. 2021 Apr 20;16(4):e0250081. doi: 10.1371/journal.pone.0250081. eCollection 2021.

Abstract

Dormancy of hematopoietic stem cells and formation of progenitors are directed by signals that come from the bone marrow microenvironment. Considerable knowledge has been gained on the murine hematopoietic stem cell microenvironment, while less so on the murine progenitor microenvironment and even less so on these microenvironments in humans. Characterization of these microenvironments is decisive for understanding hematopoiesis and finding new treatment modalities against bone marrow malignancies in the clinic. However, it is equally challenging, because hematopoietic stem cells are difficult to detect in the complex bone marrow landscape. In the present study we are characterizing the human hematopoietic stem cell and progenitor microenvironment. We obtained three adjacent bone marrow sections from ten healthy volunteers. One was used to identify a population of CD34+/CD38- "hematopoietic stem cells and multipotent progenitors" and a population of CD34+/CD38+ "progenitors" based on immunofluorescence pattern/intensity and cellular morphology. The other two were immunostained respectively for CD34/CD56 and for CD34/SMA. Using the combined information we performed a non-computer-assisted quantification of nine bone marrow components (adipocytes, megakaryocytes, bone surfaces, four different vessel types (arteries, capillaries, sinusoids and collecting sinuses), other "hematopoietic stem cells and multipotent progenitors" and other "progenitors") within 30 μm of "hematopoietic stem cells and multipotent progenitors", "progenitors", and "random cell profiles". We show that the microenvironment of the "hematopoietic stem cells and multipotent progenitors" is significantly enriched in sinusoids and megakaryocytes, while the microenvironment of the "progenitors" is significantly enriched in capillaries, other "progenitors", bone surfaces and arteries.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes
  • Adult
  • Aged
  • Antigens, CD34
  • Bone Marrow / metabolism
  • Bone Marrow Cells / cytology*
  • Bone Marrow Cells / metabolism
  • Bone Marrow Cells / physiology
  • Cell Differentiation
  • Cell Separation
  • Cells, Cultured
  • Female
  • Flow Cytometry
  • Hematopoiesis
  • Hematopoietic Stem Cell Transplantation
  • Hematopoietic Stem Cells / cytology*
  • Hematopoietic Stem Cells / metabolism
  • Hematopoietic Stem Cells / physiology
  • Humans
  • Immunophenotyping
  • Megakaryocytes
  • Membrane Glycoproteins
  • Middle Aged
  • Stem Cell Niche / physiology*

Substances

  • Antigens, CD34
  • Membrane Glycoproteins

Grants and funding

HBK received the following grants. The Southern Region research post.doc. grant, no. 1362409; the Zealand and Southern Region common research grant, no. 14-001308; Overlaege Joergen Werner Schous og hustru Else Marie Schou, født Wonges, fond no. 85832. The funders did not play any role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.